Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Apr;53(4):493-502.
doi: 10.1097/SHK.0000000000001370.

Microvascular and Systemic Impact of Resuscitation with PEGylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch in a Rat Model of Transient Hemorrhagic Shock

William H Nugent  1 , Forest R Sheppard  2 , Michael A Dubick  3 , Ramon F Cestero  4 , Daniel N Darlington  3 , Ronald Jubin  5 , Abe Abuchowski  5 , Bjorn K Song  1
Affiliations

Microvascular and Systemic Impact of Resuscitation with PEGylated Carboxyhemoglobin-Based Oxygen Carrier or Hetastarch in a Rat Model of Transient Hemorrhagic Shock

William H Nugent et al. Shock. 2020 Apr.

Abstract

Background: Hemorrhage is the leading cause of preventable, traumatic death. Currently, prehospital resuscitation fluids provide preload but not oxygen-carrying capacity-a critical blood function that mitigates microvascular ischemia and tissue hypoxia during hemorrhagic shock. Solutions containing polymerized hemoglobin have been associated with vasoactive and hypertensive events. A novel hemoglobin-based oxygen carrier, modified with PEGylation and CO moieties (PEG-COHb), may overcome these limitations.

Objectives: To evaluate the systemic and microcirculatory effects of PEG-COHb as compared with the 6% hetastarch in a rat model of hemorrhagic shock.

Methods: Male Sprague Dawley rats (N = 20) were subjected to severe, controlled, hemorrhagic shock. Animals were randomized to 20% estimated blood-volume resuscitation with either 6% hetastarch or PEG-COHb. Continuous, invasive, cardiovascular measurements, and arterial blood gases were measured. Microcirculatory measurements of interstitial oxygenation (PISFO2) and vasoactivity helped model oxygen delivery in the spinotrapezius muscle using intravital and phosphorescence quenching microscopy.

Results: Hemorrhage reduced mean arterial pressure (MAP), arteriolar diameter, and PISFO2, and increased lactate 10-fold in both groups. Resuscitation with both PEG-COHb and hetastarch improved cardiovascular parameters. However, PEG-COHb treatment resulted in higher MAP (P < 0.001), improved PISFO2 (14 [PEG-COHb] vs. 5 [hetastarch] mmHg; P < 0.0001), lower lactate post-resuscitation (P < 0.01), and extended survival from 90 to 142 min (P < 0.001) as compared with the hetastarch group.

Conclusions: PEG-COHb improved MAP PISFO2, lactate, and survival time as compared with 6% hetastarch resuscitation. Importantly, hypertension and vasoactivity were not detected in response to PEG-COHb resuscitation supporting further investigation of this resuscitation strategy.

PubMed Disclaimer

References

    1. Eastridge BJ, Hardin M, Cantrell J, Oetjen-Gerdes L, Zubko T, Mallak C, Wade CE, Simmons J, Mace J, Mabry R, et al. Died of wounds on the battlefield: causation and implications for improving combat casualty care. J Trauma 71: (1 suppl): S4–8, 2011.
    1. Ball CG. Damage control resuscitation: history, theory and technique. Can J Surg 57 (1):55–60, 2014.
    1. Fodor GH, Babik B, Czovek D, Doras C, Balogh AL, Bayat S, Habre W, Petak F. Fluid replacement and respiratory function: comparison of whole blood with colloid and crystalloid: A randomised animal study. Eur J Anaesthesiol 33 (1):34–41, 2016.
    1. Nugent WH, Cestero RF, Ward K, Jubin R, Abuchowski A, Song BK. Effects of sanguinate (R) on systemic and microcirculatory variables in a model of prolonged hemorrhagic shock. Shock 52: (Suppl 1): 108–115, 2019.
    1. Liu LM, Ward JA, Dubick MA. Effects of crystalloid and colloid resuscitation on hemorrhage-induced vascular hyporesponsiveness to norepinephrine in the rat. J Trauma 54: (5 suppl): S159–S168, 2003.

Publication types

LinkOut - more resources